Cancer immunotherapy using virus particles and immune checkpoint therapy

21:

• An intratumoral immunotherapy for treating cancer in a subject, comprising:
• therapeutically effective amounts of a cowpea mosaic virus or a cowpea mosaic virus-like particles and an immune checkpoint therapy formulated for in situ administration to cancer of the subject, wherein the cowpea mosaic virus or cowpea mosaic virus-like particles are not used as a vehicle for drug or antigen delivery.

22:

• The intratumoral immunotherapy of claim 21, wherein the immune checkpoint therapy comprises a positive or stimulatory immune checkpoint modulating agent.

23:

• The intratumoral immunotherapy of claim 22, wherein the positive immune checkpoint modulating agent is an OX40 (CD134) agonist.

24:

• The intratumoral immunotherapy of claim 23, wherein the OX40 agonist is an agonistic anti-OX40 monoclonal antibody.

25:

• The intratumoral immunotherapy of claim 21, wherein the immune checkpoint therapy comprises a negative or inhibitory immune checkpoint modulating agent.

26:

• The intratumoral immunotherapy of claim 25, wherein the negative or inhibitory immune checkpoint modulating agent is a programmed cell death protein 1 (PD-1) inhibitor.

27:

• The intratumoral immunotherapy of claim 26, wherein the PD-1 inhibitor is an inhibitory anti-PD-1 monoclonal antibody.

28:

• The intratumoral immunotherapy of claim 21, wherein the cowpea mosaic virus or cowpea mosaic virus-like particles stimulate an anti-tumor response through recruitment of monocytes into a tumor microenvironment (TME), promotes signaling of the IFN-gamma pathway, and/or increase recruitment of tumor infiltrating neutrophils (TIN) and natural killer cells.

29:

• The intratumoral immunotherapy of claim 21, wherein the cowpea mosaic virus or a cowpea mosaic virus-like particles upon in situ administration to the cancer increases the expression of checkpoint regulators on Foxp3− CD4+ effector T cells in the tumor microenvironment.

30:

• The intratumoral immunotherapy of claim 21, wherein the cowpea mosaic virus or a cowpea mosaic virus-like particles upon in situ administration to the cancer increases recruitment of tumor infiltrating lymphocytes (TILs) at a tumor site of the subject.

31:

• The intratumoral immunotherapy of claim 30, wherein the tumor infiltrating lymphocytes (TILs) are tumor infiltrating neutrophils (TINs).

32:

• The intratumoral immunotherapy of claim 21, wherein in situ administration of the cowpea mosaic virus or a cowpea mosaic virus-like particles and the immune checkpoint therapy increase tumor infiltration by antitumor neutrophils/macrophages, natural killer cells, and CD4+ and CD8+ effector T cells and inhibits immunosuppressive cells in the tumor microenvironment.

33:

• The intratumoral immunotherapy of claim 21, wherein administration of the cowpea mosaic virus or a cowpea mosaic virus-like particles and an immune checkpoint therapy has a synergistic effect on the antitumor response of TILs at a tumor site of the subject.

34:

• The intratumoral immunotherapy of claim 21, wherein the cowpea mosaic virus or a cowpea mosaic virus-like particles and the immune checkpoint modulating agent are formulated for intratumoral injection.

35:

• The intratumoral immunotherapy of claim 21 wherein the cancer is selected from the group consisting of melanoma, colon cancer, and ovarian cancer.